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YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA DECEMBER 2016

Conference news: Q & A with


IOF Regionals 2016 perinatal psychiatrist
& AFCC 2016 Dr Helen Chen

a novel option
for TNFi-refractory Crohn’s disease
CONTENTS
MIMS DOCTOR - YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA Managing Editor
Elvira Manzano

Contributing Editors
Roshini Claire Anthony, Pearl Toh,
Stephen Padilla, Jairia dela Cruz,
Elaine Soliven, Alex Ngai, Pearly Neo,
Christina Lau, Jackey Suen, Joseph Robles

Designer
DECEMBER ISSUE Peggy Tio

Cover Story Production


Edwin Yu, Ho Wai Hung, Agnes Chieng

Circulation Executive
5 Ustekinumab a novel option for TNFi-refractory Crohn’s disease Christine Chok

Accounting Manager
Conference Coverage Minty Kwan
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016), Singapore Advertising Coordinator
7 Oestradiol depletion linked to bone structure decline Rachael Tan

CEO
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8 Long-term osteoporosis treatment should be for those with highest fracture risk
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COVER STORY

Ustekinumab
a novel option
for TNFi-refractory Crohn’s disease
COVER STORY

ELVIRA MANZANO

T
he monoclonal antibody usteki-
numab induces clinical response
and maintains remission in mod-
erate-to-severe Crohn’s disease that
is refractory to tumour necrosis factor
inhibition (TNFi) or standard therapy,
according to three pivotal studies,
widening the treatment options for this
chronic inflammatory condition.

“Patients with Crohn’s had limited


treatment options previously, so this


is a big advance,” said study author
Professor William Sandborn from the
University of California in San Diego, Clinical response was defined in
California, US. “[Ustekinumab] is also
“Patients with Crohn’s both studies as a reduction from base-
very convenient for patients – the had limited treatment line of 100 points in the Crohn’s Dis-
maintenance dosing is only once every options previously, ease Activity Index (CDAI) or a CDAI
8 weeks and patients can inject them- so this is a big advance” score of <150.
selves.”
— Prof William Sandborn The phase III study, IM-UNITI, in-
Ustekinumab is an interleukin-12/23 volving 397 responders in the induc-
inhibitor approved for the treatment of tion trials showed that 53 percent of
plaque psoriasis and psoriatic arthritis, “There was no increase in the rates of patients treated with subcutaneous
and recently Crohn’s disease, a com- serious infection or cancer compared maintenance injections of ustekinum-
plex disease of the ileum and the colon with placebo.” ab 90 mg every 8 weeks achieved re-
for which currently there is no cure. No mission at 44 weeks compared with
one treatment works for every patient Trials support 36 percent of those receiving a place-
and the goals of therapy are to reduce ustekinumab’s approval bo (p=0.005).
inflammation to ease diarrhoea, rectal Studies have demonstrated usteki-
bleeding, abdominal pain and other numab’s efficacy in patients who had In patients receiving ustekinumab
symptoms, and bring about long-term failed TNF antagonists or conventional every 12 weeks, 49 percent were in re-
remission. therapies. In the UNITI-1 study of 741 mission vs 36 percent in those receiv-
Crohn’s disease patients (median dis- ing a placebo (p=0.04). Adverse events
In two induction trials of ustekinum- ease duration, 10 years) with a history such as headache, nausea, arthralgia
ab, patients receiving two single doses of TNF failure and treated with intrave- and infections were similar for placebo
of intravenous ustekinumab (130 mg or nous ustekinumab (130 mg or 6 mg/ and ustekinumab maintenance therapy,
approximately 6 mg/kg of body weight) kg), the rates of response at week 6 which were consistent with safety trials
had significantly higher response rates were significantly higher with usteki- of ustekinumab in psoriatic arthritis.
at week 6 vs those on placebo. In the numab (34.3 and 33.7 percent) than
maintenance trial, initial responders with placebo (21.5 percent; p≤0.003 “The findings suggest that usteki-
treated with subcutaneous ustekinum- for both). numab has a long duration of action,
ab (90 mg every 8 weeks or every 12 a likelihood that may become better
weeks) had greater benefit at 44 weeks In the UNITI-2 study of 628 patients understood in future trials,” said the re-
vs those given placebo. [N Engl J Med (median disease duration, 6 years) who searchers.
2016; 375:1946-1960;doi: 10.1056/ had been treated unsuccessfully with im-
NEJMoa1602773] munosuppressives and corticosteroids Experts said further investigation
but not TNF-blockers, or who had ex- is clearly warranted to determine
“Ustekinumab is effective, leading perienced unacceptable side effects, re- how long would remission last. The
to a clinical remission [relief from ab- sponse rates were 51.7 and 55.5 percent disease often recurs, frequently near
dominal pain and diarrhoea] in moder- for ustekinumab doses at week 6 vs 28.7 the reconnected tissue, even after
ate-to-severe Crohn’s,” said Sandborn. percent for placebo (p<0.001 for both). surgery.

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DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Oestradiol depletion in premenopausal


women with breast cancer linked to
bone structure decline
PEARL TOH

O
estradiol depletion in pre-
menopausal women with early
breast cancer who were treat-
ed with ovarian suppression (OS) plus
aromatase inhibition (AI) endocrine
therapy was associated with severely
deteriorated cortical and trabecular mi-
crostructure in their bones, according
to preliminary data of an ongoing study.

“[The] severe and perhaps irrevers-


ible microstructural deterioration and Cases treated with OS+AI had the researchers, although these were
the longevity of these women suggest higher cortical porosity in the distal not included in the presentation.
there is a need to investigate the role radius in all measured outcomes of
of early intervention to preserve bone porosity including total cortex, com- Previous studies have shown that
strength,” said researchers from the pact cortex, outer and inner transi- oestrogen deficiency can increase
Departments of Endocrinology and tional zones, and lower MMD than bone remodelling rate by increasing
Medicine at Austin Hospital in Heidel- premenopausal age-matched controls the lifespan of osteoclasts while de-
berg, Victoria, Australia. (p<0.001 for all). creasing that of osteoblasts. (Endo-
cr Rev 2000;21:115-137) The rapid
The case-control study enrolled 23 Despite being almost two decades remodelling will reduce MMD and
premenopausal cases (mean age 42.3 younger than women who were 10 eventually lead to severe microstruc-
years) with breast cancer who were years postmenopause, cases had tural deterioration, according to the
treated with OS+AI for a median dura- similar cortical porosity in all mea- researchers.
tion 1.5 years, 42 healthy age-matched sured outcomes mentioned above in
premenopausal women (mean age the distal radius as postmenopausal
44.4 years), and 35 healthy women controls.
who were 10 years post natural meno-
pause (mean age 62.4 years). MMD was also significantly lower in
Scan the
premenopausal cases than postmeno-
QR code for full
Women who had been on tamoxifen pausal controls (p<0.001).
coverage of IOF
therapy for >6 months or prior bone-re-
Regionals
lated therapy were excluded from the In addition, trabecular bone volume
2016
study. [IOF 2016, abstract P174] (BV/TV) in the distal radius was 1.47
percent lower in cases compared with
Microarchitecture and matrix min- premenopausal controls (p=0.008),
eral density (MMD) of distal radius and and 0.67 percent lower compared with
tibia were assessed using high-resolu- postmenopausal controls (p=0.07),
tion peripheral quantitative computed which was due to fewer but not thinner
tomography. OS+AI endocrine thera- trabeculae.
py for breast cancer led to more rapid
oestradiol depletion than natural meno- Similar results were also seen for
pause, said the researchers. measurements in the tibia, according to

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DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Long-term osteoporosis treatment should be


reserved for those with highest fracture risk
ROSHINI CLAIRE ANTHONY

O
FREEDOM Extension study showed
steoporosis treatment should that treatment with denosumab for
not be initiated unless the pa- up to 8 years was associated with in-
tient concerned has a sufficient- creased BMD, reduced bone turnover
ly high risk of fracture, according to a markers, a low incidence of fractures,
presentation at the IOF Regionals 2016. and a consistent safety profile. [Osteo-
porosis Int 2015;26:2773-2783]
“Everything considered, optimal
long-term management of osteopo- “Clearly, long-term treatment is ef-
rosis is primarily dependent on an ini- ficacious ... [however], adherence to
tial judicious selection of patients and long-term treatment of osteoporosis is
of the most appropriate treatment for poor,” said Kaufman. Previously report-
each patient,” said Professor Jean- ed side effects of osteoporosis treat-
Marc Kaufman from the Department of ment include acute phase reactions,
Endocrinology at Ghent University Hos- gastroesophageal irritation, impaired
pital, Ghent, Belgium. [IOF Regionals renal function, hypocalcaemia, osteo-
2016, abstract PL14] necrosis of the jaw (ONJ), and atypical
femoral fracture (AFF), said Kaufman.
Prof Jean-Marc Kaufman
Reassessment of risk after 3–5
years is recommended. If during the A previous study pointed to an as-
course of reassessment we find that sociation between long-term bisphos- ment led to a decrease in BMD, while
the patient has a low fracture risk, this phonate therapy (in this study, alendro- another study showed that patients
patient should probably not have been nate) and ONJ and a potentially higher who were on zoledronic acid for 6 years
initiated on treatment to begin with, he incidence risk in the Asian population. [J maintained the benefits for up to 3
said. The key questions that should be Clin Endocrinol Metab 2014;99:2729- years after discontinuing therapy. [J Clin
asked for an individualized approach 2735] Another study noted an increased Endocrinol Metab 2011;96:3367-3373;
are what the baseline fracture risk was, incidence of AFF with longer duration J Clin Endocrinol Metab 2011;96:972-
what treatment the patient is currently of bisphosphonate use. [J Bone Miner 980; J Bone Miner Res 2015;30:934-
on and adherence to it, and what the Res 2012;27:2544-2550] 944]
reassessed present risk for new fracture
is, said Kaufman. Studies have shown “[ONJ and AFF] are associated with “For drugs such as raloxifene, teri-
that efficacy of treatment – reduced bisphosphonate use but they are rare paratide, denosumab, or odanacatib,
fracture risk – is maintained with long- occurrences and have limited impact on there is rapid offset of effect after stop-
term therapy. benefit-risk of osteoporosis treatment,” ping, and sustained fracture prevention
said Kaufman. “Concerns for risk of requires either continued treatment or
One study showed that 7 years of feared side effects like ONJ and [AFF] switching to another active treatment,”
continuous risedronate therapy led to should only play a secondary role in said Kaufman. “For at least some bis-
improvement in bone mineral density decision making,” he said. Factors that phosphonates, offset of effect is some-
(BMD), reductions in bone turnover, predict a higher risk of fracture upon what more protracted. Nevertheless,
and no evidence of loss of anti-fracture treatment discontinuation (alendronate) fracture incidence after stopping treat-
efficacy. [Calcif Tissue Int 2004;75:462- are age and a lower femoral neck BMD ment does increase compared with con-
468] Another study showed that 10 at time of discontinuation. [JAMA Intern tinued treatment, in particular in patients
years of alendronate therapy led to an Med 2014;174:1126-1134] with initially higher fracture risk,” he said.
increase in BMD, which declined upon “Further management is mainly depen-
cessation of therapy. [N Engl J Med Studies have shown that discontin- dent on risk profile of the patient and the
2004;350:1189-1199] Results from the uing risedronate or denosumab treat- type of drug the patient is using.”

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DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Continuous treatment of osteoporosis with


denosumab provides long-term benefit
PEARL TOH

D
enosumab continuously increas-
es bone mineral density (BMD)
at the spine and hip over 10
years, and long-term treatment is asso-
ciated with reduced incidence of both
vertebral and nonvertebral fractures,
according to a presentation at the IOF
Regionals 2016.

“The goal of [osteoporosis] thera-


py is to restore bone mass and bone


quality in all aspects, whatever time that
takes,” said Professor Serge Ferrari of Prof Serge Ferrari

Service of Bone Diseases at Geneva


University Hospital in Geneva, Switzer- added. “Fracture rate reduction in year
“Denosumab
land, suggesting a T-score target of -2 4 was most prominent in subjects with
to -1.5 to minimize fracture risk in the continuously increases persistently low hip BMD.”
long term. BMD at the spine and
hip over 10 years, Discussing about the 10-year data
Being highlighted was the FREE- with denosumab, Ferrari pointed out
resulting in a majority
DOM* extension trial, a multicentre that denosumab persistently increased
open-label single-arm study which fol- of subjects achieving a lumbar spine BMD and decreased new
lowed participants who had complet- nonosteoporotic T-score” vertebral fracture incidence throughout
ed the initial 3 years of the FREEDOM the 10-year extension period of the
trial for another 4 years. The extension FREEDOM study. [ASBMR** 2015, ab-
study included 4,074 postmenopausal Furthermore, the overall nonver- stract 1157]
women with osteoporosis randomized tebral fracture rate was decreased by
to either subcutaneous denosumab 21 percent during years 4–7 compared “Denosumab continuously increas-
60 mg Q6M or placebo in the initial 3 with the initial 3 years of denosumab es BMD at the spine and hip over 10
years, who were continued (ie, long- treatment in the long-term group (1.98 years, resulting in a majority of subjects
term group) or crossed-over, respec- vs 1.54, RR, 0.79; p=0.046). achieving a nonosteoporotic T-score,”
tively, to receive denosumab from years he said.
4–7 during the extension period. [Oste- Collectively, the study showed that
oporos Int 2015;26:2763-2771] treatment with denosumab beyond “As you treat longer, you need to
3 years was associated with a further balance the risk and benefit [of a ther-
Compared with the initial 3 years reduced risk of nonvertebral fracture apy],” said Ferrari, noting that there
of denosumab treatment, nonvertebral which persisted throughout 7 years was no cumulative risk of infections or
fracture rate was 25 percent lower at of continuous treatment, according to other adverse events with denosumab
year 4 in the long-term group (1.98 vs Ferrari. treatment over 8 years as shown in the
1.48, rate ratio [RR], 0.75; p=0.127). phase II study of the drug. [Osteoporos
Similarly, a significant reduction of Also, the extent of reduction in non- Int 2013;24:227-235]
21 percent in fracture rate was ob- vertebral fracture risk achieved with
*FREEDOM: Fracture REduction Evaluation of
served in the cross-over group at year denosumab appeared to be dependent Denosumab in Osteoporosis every 6 Months
4 of treatment (2.37 vs 1.2, RR, 0.79; on the femoral neck BMD achieved **ASBMR: American Society for Bone and Mineral
p=0.0046). during the initial 3-year therapy, he Research

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DOCTOR | DECEMBER ISSUE
EFA-SpDrugInfo-0915-206x276-4c.pdf 1 18/1/16 3:48 pm
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Fluoride salt, strontium ranelate up bone


mechanical properties in osteoporosis
TRISTAN MANALAC From each of the participants, iliac Treatments led to stronger back-

S
crest biopsies were collected for the scatter signals compared to the untreat-
trontium ranelate and fluo- downstream analyses. Instrumental ed patients. Healthy controls showed
ride salt, both established as neutron activation analysis was per- the strongest backscatter signals.
strategies to reduce the risk of formed to measure the concentrations
fractures in osteoporosis patients, im- of both strontium and fluoride in the iliac Finally, strontium- and fluoride-treat-
proved the mechanical properties of crest samples. ed iliac crests showed lower indenta-
the iliac crest samples of treated os- tion distances compared with untreat-
teoporosis patients compared with The concentration of strontium in ed bone samples. Similarly, those from
untreated ones, according to a new the samples correlated with the treat- healthy controls showed the shortest
study. ment period; strontium was mostly indentation distances.
found in the newly formed bone. This
A total of 37 participants were re- was not the same for fluoride.
cruited; eight were osteoporosis pa-
tients who had not received prior Bone samples from strontium- and
treatment, nine had received fluoride fluoride-treated patients had lower cor-
treatment, nine had received strontium tical porosity compared with that from
ranelate, and 11 were healthy controls untreated patients. Healthy controls
with no bone disease. showed the lowest cortical porosity.

Maintenance statin therapy tied to grip


strength decline in elderly men
JAIRIA DELA CRUZ No differences in muscle power Ying Zhu from the Faculty of Medicine

S
and physical performance—as mea- at the Chinese University of Hong Kong
tatin use in the maintenance set- sured by chair stand time and walking said.
ting may have a negative effect speed, respectively—were observed
on muscle strength in elderly between statin users and nonusers in Previous studies described an as-
men, as evidenced by a decline in grip both groups. sociation between SAMS and reduced
strength, according to the results of a quality of life in geriatric patients. Fac-
Hong Kong cohort study. The analysis involved a cohort of tors such as low BMI, renal and hepat-
2,882 community dwellers in Hong ic function decline, comorbidities, and
After 2 years, grip strength decline Kong. Of 1,433 men and 1,449 women, multiple medications all contributed to
was greater among male statin users 4 and 5 percent were continuous statin an increased risk of SAMS.
than nonusers (mean change, –1.452 users, respectively. The mean age was
vs –0.756, respectively; p=0.035). This 70.79 years in male statin users and As SAMS has become increasing-
association was not observed in fe- 71.8 years in female statin users. ly common in the geriatric population,
male subjects (mean change in grip clinicians must exercise careful judg-
strength, –1.555 among statin users The issue of statin-associated ment when prescribing statins, espe-
vs –1.107 among nonusers; p=0.061). muscle symptoms (SAMS) in the elder- cially for patients older than 80 years,
[IOF Regionals 2016, abstract OC03] ly has been largely neglected, Dr Liu- Zhu said.

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DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Smoking negatively affects total hip BMD


JAIRIA DELA CRUZ 50 years, 51 to 60 years, 61 to 70 years, years; p<0.01 and p=0.02; 81 to 90

C
71 to 80 years and 81 to 90 years). years; p=0.02 and p=0.13).
urrent smoking appears to pro- Total hip and lumbar spine BMD were
mote a significant decrease in measured and compared between the A similar trend for lumbar spine
total hip bone mass density current-smoking and noncurrent smok- BMD was observed, but only in wom-
(BMD) in older men and women, ac- ing participants. [IOF Regionals 2016, en. Current smoking women had slight-
cording to a sub-study of the Taiwan abstract 11] ly lower lumbar spine BMD compared
Osteoporosis Survey. with their noncurrent smoking counter-
Total hip BMD demonstrated a parts, with the difference not reaching
On the other hand, lumbar spine downward trend with increasing age. statistical significance across all age
BMD progressively declines with age, A significant decrease in total hip BMD groups.
regardless of smoking status, but only was observed from the age of 61 years,
in women. and the decrease was greater among The findings suggest that current
women and men who currently smoked smoking has a negative impact on total
The study population comprised than among their noncurrent smoking hip BMD, but not lumbar spine BMD,
9,667 women and 2,529 men who counterparts (61 to 70 years; p=0.01 in in both women and men in older age
were grouped according to age, (40 to women and p=0.02 in men; 71 to 80 groups.

Vit D deficiency prevalent among children


regardless of fracture history
STEPHEN PADILLA D testing and correction in the Saudi

C
paediatric population,” they added. Mean circulating 25-hydroxyvitamin
hildren with a history of bone (25OH) D level in children with a histo-
fractures have significantly low- A cross-sectional study was con- ry of fracture was significantly lower in
er levels of vitamin D than those ducted to assess the link between both boys (p<0.01) and girls (p<0.01)
without such a history, according to a serum 25-hydroxyvitamin D levels and than those without. However, both
Saudi study. fractures in Saudi children. Included groups had low mean 25(OH)D levels.
were 1,022 children without fracture Furthermore, age was positively associ-
Even without a history of fracture, history (476 boys [age 14.56 years; ated with 25-hydroxyvitamin D in boys
vitamin D status correction is needed in BMI 22.38] and 546 girls [age 13.57; (p<0.05) and negatively in girls (p<0.05)
the general Saudi paediatric population. BMI 22.24]) and 234 Saudi children with a history of fracture.
with a history of fracture (148 boys
“Our data indicate an association [aged 14.25 years; BMI 22.66] and 86 “One explanation for this observa-
between vitamin D status and bone frac- girls (aged 13.76 years; BMI 21.33). [J tion may be conservative social and re-
tures in Saudi children. Because fracture Endocrinol Invest 2016;39:1125-1130] ligious practices imposed on girls and
rates in children are increasing and bone the fact that advancing age in girls are
health status in childhood may directly Researchers collected anthropomet- more often covered compared to boys
impact adult bone health, opportunities ric and fasting serum biochemical data, of similar age,” researchers said.
to intervene during childhood should be and assessed serum 25-hydroxyvitamin
pursued,” researchers said. D level using electrochemiluminescence. Boys were also more likely to have
fracture than girls (148 vs 86). This might
“Given the high prevalence of vita- “Vitamin D levels were significantly be due to higher outdoor activities such
min D deficiency in Saudi children with lower in children with a history of fracture as sports in boys compared to girls and
and without fracture, a strong consider- in both boys and girls than those without to physiological difference in this age
ation should be given for routine vitamin such a history,” researchers concluded. group, according to researchers.

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DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) • November 4-6 • Singapore

Anxiety disorder linked to osteoporosis


STEPHEN PADILLA disorder and the subsequent develop- incidence of newly diagnosed osteopo-

P
ment of osteoporosis. Included were rosis remained significantly increased
eople with a history of anxiety 7,098 patients from the anxiety disor- within the stratified follow-up durations
disorder are more likely to have der and no-anxiety groups who were (0 to 1, 1 to 5, 5 to 10, ≥10 years).
osteoporosis, a study in Taiwan matched according to age and sex
has shown. between 2000 and 2013. Researchers Patients with anxiety disorder were
calculated the incidence rate and RRs of 1.79 times more likely to develop oste-
“The risk ratios [RRs] are highest for subsequent new-onset osteoporosis for oporosis than those without. There was
osteoporosis within 1 year of anxiety both cohorts. Cox proportional hazard also a significant increase in osteoporo-
disorder diagnosis, but the risk remains models were used to assess the effect sis risk in patients with anxiety disorder
statistically significant for more than 1 of anxiety disorder, and the Kaplan-Mei- who had comorbidities such as hyper-
year,” researchers said. er method was applied to estimate tension, diabetes mellitus and chronic
the cumulative osteoporosis incidence liver disease.
Using data from the Longitudinal curves.
Health Insurance Database 2000 of Researchers suggested that clini-
Taiwan, a population-based retrospec- Patients in the anxiety cohort had a cians should pay particular attention to
tive cohort analysis was conducted to higher risk of osteoporosis than those in osteoporotic comorbidities in patients
assess the association between anxiety the comparison cohort. In addition, the with anxiety disorder.

Lumbar muscle volume loss tied to


compression fractures
JAIRIA DELA CRUZ explored the relation between muscle Women with compression frac-

L
composition and vertebral compres- tures had significantly smaller mean
oss of paraspinal and psoas lean sion fractures, they added. sectional volume of lean muscle in the
muscle volume at the low lumbar erector spinae muscle at L3/4, L4/5,
levels appears to be related to the To address the dearth of evidence L5/S1 levels compared with controls
risk of osteoporotic/osteopenic lumbar in this area, the investigators looked (p<0.05 for all). The results were similar
compression fractures among post- at 32 postmenopausal women — 18 for the mean sectional volume of mul-
menopausal women, according to a of whom had compression fractures tifidus muscle at L4/5 and L5/S1 lev-
study. (mean age 80.1 years; mean BMI 23.2 els (p<0.05 for all). On the other hand,
kg/m2) while 14 were healthy (controls; the sectional volume of psoas muscles
Sarcopenia is a geriatric syndrome mean age 53.3 years; mean BMI 24.5 at all levels significantly differed be-
characterized by progressive decline kg/m2). tween the fracture and control groups
in muscle mass and function, and is a (p<0.05 for all).
known contributor to increased risk of MRI images of the paraspinal mus-
falls and fractures, a team of investiga- cles, multifidus and erector spinae, and
tors from the Wan Fang Hospital-Tai- psoas muscles at the lumbar disc lev- “The proportion of lean muscle
pei Medical University in Taipei, Taiwan els were obtained. Lean muscle and to total volume reflects the degree of
said. fat volume of each muscle group was fatty change and was also found to
calculated individually, and the propor- be significantly more prominent in the
Decreased strength has been impli- tion of BMI-normalized muscle and fat paraspinal muscles of [women with
cated in the loss of paraspinal muscle volumes was compared between the compression fractures] at the L5/S1
mass, but only one study has so far fracture and control groups. levels,” the investigators noted.

13
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Trimetazidine may improve


cardiac energetics and efficiency in SCAD
ELVIRA MANZANO

N
ewer metabolic agents, includ-
ing trimetazidine, represent
ancillary forms of prophylactic
antianginal therapy and may be useful
in patients with stable coronary artery
disease (SCAD) who are unsuitable for
percutaneous or surgical revasculariza-
tion, says a leading cardiologist at the
recent AFCC 2016.

“On top of its antianginal properties,


trimetazidine, administered at 35 mg
twice daily, modulates myocardial met-
abolic efficiency and is recognized as a
second-line agent in those whose angi- Prof Michel Komajda

na persists despite use of standard an-


tianginal therapy, and who are not suit- impairment of coronary blood flow,” he whom will experience angina as part of
able for invasive revascularization,” said said. “One of three chronic stable angina the disease’s clinical manifestations. The
Prof Michel Komajda from the University outpatients remains symptomatic and at pharmacological therapy is in addition to


Pierre et Marie Curie and the Pitie Sal- high risk of cardiovascular [CV] events.” lifestyle changes and risk factor control.
petriere Hospital in Paris, France. [Eur Heart J 2013;34:2949-3003]

Trimetazidine reduces the mismatch “Angina occurs when “Angina occurs when myocardial ox-
between oxygen demand and delivery ygen demand exceeds oxygen supply.
myocardial oxygen
through a shift in cardiac metabolism Trimetazidine, and other anti-ischaemic
in ischaemic conditions. “It shifts the demand exceeds oxygen agents, is being used for second-line
cardiac cell metabolism from free fatty supply. Trimetazidine, treatment and for the control of stable
acid oxidation to glucose oxidation as a and other anti-ischaemic angina episodes,” said Komajda.
source of cardiac energy and therefore,
agents, is being used for
improves cardiac efficiency,” explained
Komajda. “Potentiation of glucose ox- second-line treatment and
idation optimizes cellular energy pro- for the control of stable Scan the
cesses, maintaining proper energy me- angina episodes” QR code for
tabolism during ischaemia.” full coverage of
AFCC 2016
Despite advances in pharmaco- Treatment options vary with the pre-
therapy and revascularization strate- cise cause, and relevant to increased
gies, SCAD or stable ischaemic heart myocardial oxygen demand as against
disease, remains associated with poor reduced supply. Current guidelines on
quality of life, poor outcomes, and dis- SCAD by the European Society of Car-
ability, said Komajda. diology (ESC) recommend the use of
ACE inhibitors, statins and aspirin, and
“A significant proportion of patients medication relieving symptoms to pre-
revascularized by angioplasty still com- vent CV events, including acute cor-
plain of angina pectoris, reflecting an onary syndromes, in patients most of

14
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Combination therapy synergistically reduces


CVD and mortality risks in hypertension
PEARL TOH

A
ntihypertensive combination ther-
apy acts synergistically in reduc-
ing the risk of cardiovascular dis-
ease (CVD) and mortality, according to
data presented at the AFCC 2016.

“Hypertension is the biggest revers-


ible cause of death in the world today,”
said Professor Alistair Hall of the Heart
Research Centre at Leeds General In-
firmary in Leeds, UK, who stated that
the ultimate goal of hypertension man-
agement is to protect against CVD and
reduce mortality. Prof Alistair Hall

It was estimated that approximately by 6.0/3.0 mm Hg more in the treat- plus the ACE inhibitor perindopril was
75 percent of patients with hyperten- ment group, noted Hall. [N Engl J Med associated with reduced CV events


sion had uncontrolled blood pressure 2016;374:2009-2020] and mortality rate in patients with un-
(BP), but only 32.5 percent of those be- controlled hypertension, Hall revealed.
ing treated managed to keep their BP [Clin Drug Investig 2013;33:469-476]
under control, based on a cross-sec- “The once-daily
tional analysis of more than 142,000 dosing regimen could Not only did the synergistic ac-
adults. [JAMA 2013;310:959-968] tion of FDC with amlodipine and per-
help improve patient indopril diminish their side effects, the
According to the latest guidelines compliance and thus, once-daily dosing regimen could help
from ESH/ESC*, monotherapy is only efficacy of treatment” improve patient compliance and thus,
effective in reducing BP in a limited efficacy of treatment, said Hall.
number of hypertensive patients, [Hy-
pertens 2007;25:1105-1187] and that *ESH/ESC: European Society of Hypertension/
European Society of Cardiology
a combination of two or more drugs is “The data on the use of ARBs in the **HOPE-3: Heart Outcomes Prevention Evaluation 3
required to achieve BP control in high- HOPE-3 trial again emphasize the need
risk individuals with multiple comorbid- to recognize the lack of important car-
ities. [Eur Heart J 2013;34:2159-2219] diovascular benefits with ARBs as com-
pared with a placebo. These findings
However, the effect on BP and are in stark contrast to the benefits seen
CVD risk reduction varies with different with ACE [angiotensin-converting-en-
combination of therapies. Citing data zyme] inhibitors,” wrote Hall and co-au-
from the HOPE-3** trial, the combined thor in a separate correspondence. [N
therapy of hydrochlorothiazide plus the Engl J Med 2016;375:1190-1194]
angiotensin receptor blocker (ARB)
candesartan was not associated with “This is an important message for
a lower risk of major cardiovascular clinicians who are tasked with prepar-
events among patients with interme- ing guidelines.”
diate risk without CVD compared with On the other hand, fixed-dose com-
placebo, although the BP decreased bination (FDC) therapy with amlodipine

15
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Early cardiac MRI helps detect worsening


heart function in at-risk patients
ROSHINI CLAIRE ANTHONY

E
arly cardiac magnetic resonance
imaging (MRI) in patients with
acute ST elevation myocardial in-
farction (STEMI) can predict worsening
of left ventricular (LV) systolic function,
LV remodelling and reverse remodel-
ling, according to a study.

Participants in this prospective, ob-


servational study were patients aged
30—70 years (mean age 47.8 years)
admitted to the Sarawak General Hos-
pital Heart Centre between December
2012 and November 2014 who had
been diagnosed with acute anterior or Associate Prof Asri Said
inferior STEMI. Participants must have
achieved Thrombolysis in Myocardial daemia did not influence LV remod- According to Said, acute MI has a
Infarction (TIMI) 3 flow on a coronary elling; however, peak creatine kinase variable impact on outcome and long-
angiogram (n=101) and undergone (p=0.018) and ejection fraction at ad- term survival of patients, with an 18—
reperfusion with either percutaneous mission (p=0.025) did predict LV re- 24 percent risk of developing heart fail-
coronary intervention or thrombolysis. modelling at 6 months. ure after 30 days and up to 33 percent
at 5 years.
MRI scans were carried out within 1 Infarct size was found to be larger
week of index admission and again be- in those with LV remodelling than those “We must have a way to differentiate
tween 3 and 6 months postadmission. without (34.8 percent vs 24.8 percent; which patients require specialized care,
Individuals unable to tolerate MRIs, p=0.002); LV remodelling was 2.5 times who are the high-risk patients,” he said,
those with end-stage renal failure (esti- more likely in the case of a larger infarct commenting that this study represents
mated glomerular filtration rate <45 mL/ (≥35 percent). Forty-nine patients (48.5 a small step towards the evaluation of
min/1.7m2), severe valvular disease, or percent) experienced reverse LV re- patient-tailored therapy based on risk
a history of anaphylaxis to radiographic modelling. stratification using early cardiac MRI.
contrast were excluded from the study.
“From the MRI, we noted that pa- “This study suggests that early [car-
“The objective of my study was to tients with reverse remodelling were diac magnetic resonance imaging] is
see whether MRI was able to delineate patients with smaller infarct size,” said feasible in acute STEMI patients. In our
factors that influence LV remodelling in Said. There were 15 major adverse car- cohort, the patients with larger infarct
successfully reperfused patients de- diovascular events (MACE) including size and [microvascular obstruction
fined as TIMI 3 flow on coronary angio- four deaths, five new heart failures, one (MVO)] present experienced significant
gram,” said Associate Professor Asri new myocardial infarction (MI), and one LV remodelling and poorer LV systol-
Said from the cardiology department unplanned revascularization. ic function even after achieving TIMI
at Sarawak General Hospital, Sarawak, 3 flow on angiogram,” said Said, who
Malaysia, who presented the findings. “We identified that a larger infarct mentioned that a study using a bigger
size is a predictor for MACE ... [and] sample size over a longer follow-up pe-
Results of the study showed that the lower the ejection fraction, the more riod and incorporating analysis of ear-
age, sex, smoking, and presence of likely [the incidence of] MACE,” said ly and late MVO and oedema is in the
diabetes, hypertension, and dyslipi- Said. works.

16
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Short DTB time,


Collimation
less radiation for hybrid
reduces
angiography unit PCI
radiation
exposure
STEPHEN PADILLA

U
sing collimation to the required visu-
al fluoroscopy field significantly re-
duced exposure to radiation, which
may have important implications for the risk
of potential radiation hazards in both pa-
tients and operators, according to a study.

Fluoroscopy remains a cornerstone im-


aging technique in electrophysiology (EP)
The ACC/AHA guidelines recommend a DTB interval of no more than 90 minutes in STEMI
practice. To assess the impact of collima-
patients requiring PCI.
tion to the required field size on clinically
significant parameter of radiation exposure,
ELVIRA MANZANO Tan Tock Seng Hospital, Singapore, researchers conducted a hospital-based

P
which could be due to a slight differ- comparative study in the Cardiac Cathe-
rimary percutaneous coronary ence in the field of view between the terization Laboratory of Cardiology Depart-
intervention (PCI) can be safe- two angiographic systems (16cm2 ment at Yangon General Hospital.
ly performed in a hybrid angi- for hybrid vs 15cm2 for conven-
ography unit without compromising tional). They sought to investigate The study involved 72 EP procedures
door-to-balloon (DTB) time and with if there is any dose difference be- performed by a team of cardiologist, a
less radiation, according to a Singa- tween emergency interventional pro- nurse, an X-ray technician, and an EP tech-
pore study. cedures performed in a hybrid vs a nician. Of these, 35 procedures were per-
conventional angiography unit (21 formed with collimation and 37 without.
Mean fluoroscopy time was re- cases each). Acquisition protocol [AFCC 2016, abstract MP3]
markably similar between the hybrid for both systems were similarly cal-
angiography unit and the convention- ibrated. Fluoroscopy and DTB time An Optically Stimulated Luminescence
al angiography unit (17.66 vs 20.06 were compared, as well as X-ray skin Dosimeter was used to measure radiation
mins) as was X-ray time (p=0.43). The dose. doses. Radiation dose per minute of flu-
DTB time was 55 mins in the hybrid oroscopy time was determined between
unit vs 52 mins in the conventional Interventional cardiologists move each study group.
angiography unit. However, there was with precision to save patient lives.
a significant difference in the X-ray Emergency PCI should be carried There were significant reductions in ra-
skin dose between the two groups at out in the shortest DTB time. The diation exposure in the collimation group.
486.76 and 705.71 mGy, respective- American College of Cardiology The greatest reduction was seen in the car-
ly. [AFCC 2016, abstract P17] and the American Heart Association diologist (0.0796 mSv per procedure or 57
(ACC/AHA) guidelines recommend a percent reduction). The X-ray technician,
This means less radiation expo- door-to-balloon interval of no more EP technician, and nurse had estimated ra-
sure to the patient, wrote research- than 90 minutes in patients with ST diation dose per minute of 0.0065 (46 per-
ers Neil Wilkinson and Paul JL Ong segment elevation myocardial infarc- cent), 0.0071 (34 percent), and 0.0072 (37
from the Department of Cardiology, tion (STEMI) requiring primary PCI. percent), respectively.

17
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Individualized approach to reduce


CV risk in diabetes patients
PEARL TOH It was likely that long-term per- Additionally, Mbanya noted that

G
spective and selection of patients were these cohorts had a long duration of
lucose control must remain required to reveal the benefits, he sug- T2D (10 years), in contrast with the
at the core of type 2 diabetes gested. newly diagnosed patients included in
(T2D) management but requires the UKPDS.
an individualized approach to help re- “It takes time to observe a signifi-
duce cardiovascular (CV) events, ac- cant benefit of glucose control on mi- Drawing from lessons learnt from
cording to data presented at the AFCC crovascular complications,” Mbanya these studies, several factors to be
2016. said, referring to the UKPDS* which considered when personalizing glu-
found that the risk for microvascular cose targets include diabetes dura-
Glycaemic control should still be disease, including retinopathy and ne- tion, history of glucose control (ie, risk
the focus of T2D management in order phropathy, was significantly reduced of hypoglycaemia), pre-existing CVD,
to avoid acute complications such as in T2D patients who received intensive comorbidities, frailty, life expectan-
dehydration, osmolarity, and infections glucose therapy (eg, sulfonylurea or cy for performing intensive glucose
that could arise with severe chronic hy- insulin) compared with those receiving control for more than 5 years, and
perglycaemia, and to optimize the pre- conventional dietary intervention, and patient’s preference. [Diabetes Care
vention of micro- and/or macrovascu- this benefit persisted for 10 years af- 2016;39:S187-S195]
lar complications, said Professor Jean ter the trial (p=0.001). [N Engl J Med
Mbanya from the University of Yaoundé 2008;359:1577-1589] “[There is] no one size fits all when
in Yaoundé, Cameroon. managing diabetes,” said Mbanya, call-
The study also demonstrated sig- ing for clinicians to individualize patient
While the incidence of microvas- nificantly reduced risks for myocardi- care in terms of setting glucose target
cular events and associated complica- al infarction (15 percent; p=0.01) and and treatment intensification strategy.
tions had been shown to be reduced death from any cause (13 percent;
with controlled glucose levels in T2D, p=0.007) at 10 years follow-up. This “Overly aggressive control in old-
protective benefits on macrovascular was in contrast with the results from the er patients with more advanced dis-
events remained uncertain, especially ACCORD** and VADT*** studies, which ease may not have significant benefits
on coronary heart disease events, said found either increased or no change in and may indeed present some risk,”
Mbanya. death risk with intensive glucose ther- he cautioned, citing recommenda-
apy. [N Engl J Med 2008;358:2545- tions stated in the ADA# and EASD##
2559; N Engl J Med 2009;360:129- latest position paper. [Diabetologia
139; Lancet 2010;376:419-430] 2015;58:429-442]

“A more modest benefit [on mac-


rovascular events] is likely to be pres-
ent, but probably emerges only after
many years of improved control,” said
Mbanya.

However, the ACCORD and VADT


studies included high-risk T2D pa-
*UKPDS: UK Prospective Diabetes Study
tients with established cardiovascular **ACCORD: Action to Control Cardiovascular Risk
disease (CVD), which might have lim- in Diabetes
ited the protective benefits of intensive ***VADT: Veteran’s Affairs Diabetes Trial
#ADA: American Diabetes Association
glucose lowering on mortality and CV ##EASD: European Association for the Study of
events. Diabetes
Prof Jean Mbanya

18
DOCTOR | DECEMBER ISSUE
CONFERENCE COVERAGE
ASEAN Federation of Cardiology Congress (AFCC) • October 10-14 • Yangon, Myanmar

Strain imaging potentially useful in


detecting right ventricular dysfunction
ROSHINI CLAIRE ANTHONY

S
train imaging is an alternative,
noninvasive method suitable
for detecting right ventricular
(RV) dysfunction in repaired Tetralogy
of Fallot (TOF) patients, though not a
replacement for cardiac magnetic res-
onance imaging (MRI), according to a
study.

“RV function has been shown to


be a major determinant of clinical out-
come in congenital heart disease pa-
tients,” said Dr Lorielyn Mandigma from
the Golden Gate General Hospital in
Batangas, Philippines, who presented


RV strain imaging can complement echocardiographic assessment of repaired TOF patients.
the findings.

However, according to Mandigma, the RV free wall (RVFW) mid-segment


measurement of RV function is not al- “Accurate assessment strain and -20.66 percent of the glob-
ways easy to perform, and MRI remains of RV function might be al longitudinal strain enabled detec-
the gold standard and reference meth- tion of RV dysfunction, defined in this
important for the optimal
od to evaluate volume and ventricular study as cardiac MRI-derived RVEF
function. timing of RV outflow <50 percent.
revalvulation, especially
To determine the accuracy and cut- because [RV ejection The cut-off values for RV dysfunc-
off values of RV strain imaging parame- tion detection were both sensitive at
fraction (RVEF)] is now
ters that would detect RV dysfunction, 83.33 percent and specific at 100 per-
Mandigma and colleagues conducted being used as one of the cent, said Mandigma. The findings also
criteria influencing the validated the correlation between the
timing of pulmonary valve global and regional RV strain (the extent
of regional shortening and thickening)
replacement ”
and strain rate (rate at which deforma-
tion takes place) with cardiac MRI-de-
rived RVEF, she said.
a prospective, cross-sectional study
involving 22 patients (mean age 16.7 Nonetheless, Mandigma cautioned
years) from the Philippine Heart Cen- that RV strain imaging is not yet a sur-
tre between August 2015 and January rogate for cardiac MRI in determining
2016. Patients underwent cardiac MRI RVEF, but the utilization of RV strain
and two-dimensional strain imaging on imaging can complement the current
the same day. echocardiographic assessment of re-
paired TOF patients as well as accu-
Results of the study showed that rately predict the presence of RV dys-
cut-off values of -16.25 percent for function.
Dr Lorielyn Mandigma

19
DOCTOR | DECEMBER ISSUE
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MIMSmobileapp-206x276-0816.indd 1 22/8/16 3:22 pm


NEWSBITES

Use of bedtime media device tied to poorer


sleep in children and teens
PEARL TOH

U
se of screen-based mobile de-
vices near bedtime, or even the
mere presence of them, was as-
sociated with poorer sleep health and
excessive daytime sleepiness in chil-
dren aged 6–19 years, revealed a me-
ta-analysis of recent studies.

“Portable mobile and media devic-


es have become a ubiquitous part of
children’s lives,” noted researchers.

“The use of mobile media devic-


es at bedtime provides socially and
physiologically stimulating material
at a time when the transition to sleep
requires the brain to wind down,”
said Drs Charles Czeisler and There-
sa Shanahan from Harvard Medical
School in Boston, Massachusetts,
US, in a separate editorial. [JAMA Pe-
diatr 2016;doi:10.1001/jamapediat-
rics.2016.2986]
to further delay sleep onset and restrict Technologies that restrict service
Among the 125,198 children and sleep duration on subsequent nights,” between prespecified hours of the day
adolescents (mean age, 14.5 years) said Czeisler and Shanahan. or allow only a maximum duration of
from 20 cross-sectional studies includ- media use daily, or software programs
ed in the meta-analysis, those who In addition, when mobile devices that reduce light intensity emitted from
used portable media devices at bed- were present in the bedroom (even with- screens of media devices can help re-
time were more than twice as likely to out use) at night for at least three times inforce consistent bedtimes, according
have inadequate sleep, defined as <9 per week, there was increased likelihood to Czeisler and Shanahan.
and <10 hours of daily sleep for chil- of having inadequate sleep (OR, 1.79;
dren and adolescents, respectively, p<0.001), poorer sleep quality (OR, “Increasing awareness of guidance
than those who did not use these de- 1.53; p=0.009), and excessive daytime and technology that assist parents,
vices (odds ratio [OR], 2.17; p<0.001). sleepiness (OR, 2.27; p<0.001) among educators, healthcare professionals,
[JAMA Pediatr 2016;doi:10.1001/ja- the children and adolescents compared and policy makers in balancing the
mapediatrics.2016.2341] with those not exposed to such devices. benefits and reducing the risks of
mobile media in children is important
They were also more likely to have “Interventions should be devel- for this and future generations,” they
poor sleep quality, which referred to fre- oped and evaluated to reduce media added.
quent difficulty in initiating or maintaining device access and use at bedtime,”
sleep or having a nonrefreshing sleep said the researchers. “We support Due to the self-reported data and
(OR, 1.46; p=0.003), and excessive age-specific guidance for media de- nonrandomized studies included in the
daytime sleepiness (OR, 2.72; p=0.007). vice access and use and parent-led analysis, substantial heterogeneity was
initiatives to reduce device access and present and thus, the findings should
“Delays in sleep initiation can set use in collaboration with teachers and be interpreted with caution, according
off a reinforcing physiological cascade healthcare professionals.” to the researchers.

21
DOCTOR | DECEMBER ISSUE
NEWSBITES

Novel drug for chronic HBV gets US FDA nod


ELVIRA MANZANO

T
he US Food and Drug Admin-
istration (FDA) has approved
tenofovir alafenamide (TAF), a
nucleoside analog reverse transcrip-
tase inhibitor, as a single agent for the
treatment of chronic hepatitis B virus
(HBV) infection in adults with com-
pensated liver disease.

The approval represents an import-


ant development for people living with
chronic hepatitis B, said Professor Cal-
vin Pan, an investigator in the TAF trials
from the New York University Langone
Medical Center, New York, US.

TAF’s approval was based on a 48-


week data from two parallel phase III
studies (108 and 110), which showed
that TAF had similar efficacy profile to,


and at a dose less than one-tenth that
of, Gilead Sciences’ other anti-hep
B drug, tenofovir disoproxil fumarate TAF or TDF for 96 weeks, to be followed
(TDF), in treatment-naïve and treat- by a 48-week open-label extension in
“The approved dosing
ment-experienced adults with chronic which all participants were given TAF.
HBV infection. for TAF was 25 mg once
The primary endpoint was efficacy daily, much lower than
The approved dosing for TAF was at 48 weeks, defined as the proportion TDF’s dosing of 300 mg.
25 mg once daily, much lower than of patients whose HBV DNA was below
This means less adverse
TDF’s dosing of 300 mg. This means 20 IU/mL of blood. Secondary end-
less adverse effects on the kidney and points included bone and renal safety effects on the kidney
bone due to lower plasma levels of the parameters. and bone due to lower
drug while exerting similar antiviral effi- plasma levels of the drug
cacy as the older TDF. In the HBeAg-negative study, 94
while exerting similar
percent of those on TAF and 93 percent
TAF’s label will carry a boxed warn- of those on TDF reached the endpoint antiviral efficacy as
ing citing risks of lactic acidosis/severe whereas in the HBeAg-positive study, the older TDF”
hepatomegaly with steatosis and post- 64 percent and 67 percent, respective-
treatment severe acute exacerbation ly, reached the endpoint. Both studies
of hepatitis B. The new HBV treatment met the primary endpoint of noninferi-
is not recommended for patients with ority to TDF at 48 weeks of treatment. Normalization of serum alanine
HBV/HIV-1 coinfection. [International Liver Congress 2016, ab- aminotransferase, a measure of liver
stracts GS06 and GS12] damage, was also numerically higher
Studies 108 and 110 included in those taking TAF. The most common
1,298 patients, with 425 in the e-anti- An integrated analysis of both stud- adverse events reported were head-
gen (HBeAg)-negative study and 873 in ies found improvements in bone and ache, abdominal pain, fatigue, cough,
the e-antigen (HBeAg)-positive study, renal safety parameters in patients nausea, and back pain, with similar
randomized in a 2:1 fashion to receive treated with TAF vs TDF. rates in those receiving TAF or TDF.

22
DOCTOR | DECEMBER ISSUE
NEWSBITES

Timing of
Oat fibre lowers LDL-C,
eczema onset
other markers of CVD risk
influences food
allergy risk
PEARL TOH although this association was not

E
observed with non-HDL-C and apoB.
ating oats not only lowers
low density lipoprotein cho-
Also, reduction in LDL-C levels
lesterol (LDL-C) levels, but
in trials that administered ≥3.0 g/
also reduces levels of non-high
day of oat β-glucan was almost
density lipoprotein cholesterol
double that of studies that admin-
(non-HDL-C) and apolipopro-
istered <3.0 g/day (p=0.051), sug-
tein B (apoB), markers known to
gesting that the greater the intake of
be more closely associated with
oat β-glucan, the lower the LDL-C
cardiovascular disease (CVD) risk
levels.
than LDL-C, according to a new
meta-analysis.
“These results further support JAIRIA DELA CRUZ

T
the health claims set by Health Can-
“The appreciation of these mark- ada and US FDA that cholesterol he risk of developing food allergy at
ers for CVD risk is especially import- lowering can be achieved with a the age of 3 years is high among in-
ant in adults with metabolic syn- minimum of 3 g/day of oat β-glu- fants whose eczema occurred within
drome and/or diabetes as LDL-C is can,” the researchers said. “Inclu- the first 4 months of life, according to the
not typically elevated in this popula- sion of oat-containing foods may results of T-CHILD* study.
tion,” said the researchers. be a strategy for achieving targets in
CVD reduction.” “Our findings may contribute to a better
Participants taking a median understanding of the timing of eczema onset
dose of 3.5 g/day of the oat fibre The meta-analysis included 58 as a potentially modifiable risk factor and to
β-glucan for a median duration of 6 randomized clinical trials (38 with defining those who may need to be on guard
weeks had significantly reduced lev- parallel design and 20 with cross- for food allergy,” said researchers from the
els of LDL-C by 4.2 percent (-0.19 over design) lasting for at least 3 National Center for Child Health and Devel-
mmol/L; p<0.00001), non-HDL-C weeks (median duration of 6 weeks) opment in Tokyo, Japan.
by 4.8 percent (-0.20 mmol/L; and involving a total of 3,974 partic-
p<0.00001), and apoB by 2.3 per- ipants aged 10–67 years who were Of the 1,330 children included in the
cent (-0.03 mmol/L; p<0.0001) generally middle-aged (median age analysis, 27.9 percent developed eczema in
compared with those on a control 50.6 years). the first year of life. Eczema was associat-
diet. [Br J Nutr 2016;116:1369- ed with parental history of allergic diseases
1382] Due to the large number of trials (p<0.01), pet ownership (p=0.03), and annual
included, there was considerable household income (p<0.01). [J Dermatol Sci
Meta-regression analysis showed unexplained heterogeneity in the 2016;84:144–148]
that the higher the baseline LDL-C, meta-analysis, which the authors
the greater the effects of oat β-glu- said was inevitable. Food allergy symptoms occurred at some
can on LDL-C reduction (p=0.004), point within the response period in 7.5 per-
“There is a need for larger, lon- cent of 1,311 children with follow-up data at
ger, high-quality randomized clinical 1 year of age and in 7.5 percent of 1,136 of
trials on the effect of oat β-glucan those with follow-up data at 3 years of age.
on blood cholesterol levels, espe-
cially non-HDL-C and apoB end Eczema during the first year of life was
points, and in participants with dif- associated with a nearly fourfold risk of devel-
ferent metabolic phenotypes,” said oping food allergy at 3 years (adjusted odds
the researchers, although they be- ratio [aOR], 3.90; p<0.001).
lieved that their findings were largely
generalizable. *T-CHILD: Tokyo Children’s Health, Illness and Development

23
DOCTOR | DECEMBER ISSUE
NEWSBITES

SSRIs may increase risk of metabolic


abnormalities in patients with
schizophrenia or bipolar disorder
ROSHINI CLAIRE ANTHONY

I
ndividuals with schizophrenia or bi-
polar disorder who are on selective
serotonin reuptake inhibitors (SS-
RIs) may have an increased risk for
metabolic abnormalities, a study from
Norway shows.

After adjusting for all poten-


tial confounders, each defined dai-
ly dose (DDD) of an SSRI per day
was associated with a 3.94 mg/dL
elevation in total cholesterol levels
(95 percent confidence interval [CI],
0.35–7.50 mg/dL; p=0.032). [J Clin
Psychopharmacol 2016;doi:10.1097/
JCP.0000000000000582]

Compared with individuals not us-


ing SSRIs (serum concentration=0), a syndrome (adjusted odds ratio [ad- and metabolic abnormalities in patients
serum SSRI concentration in the mid- jOR], 2.10, 95 percent CI, 1.21–3.62; with schizophrenia or bipolar disor-
dle of the reference interval was asso- p=0.008), but not SSRI dose (ad- der,” they said, though they cautioned
ciated with a 14.56 mg/dL elevation in jOR, 1.16, 95 percent CI, 0.49–1.41; against drawing any firm conclusions
total cholesterol levels (95 percent CI, p=0.150). as causality was not established in this
5.27–23.85 mg/dL; p=0.002). study.
Previous studies have demonstrat-
Both SSRI serum concentration ed an increased risk for cardiovascular Study participants were 1,301 in-
and dose were associated with eleva- disease in individuals with schizophre- dividuals aged 18–65 years diagnosed
tions in low-density lipoprotein (LDL) nia and metabolic disease in individu- with schizophrenia or bipolar disorder
cholesterol (8.50 mg/dL, 95 percent CI, als with bipolar disorder, though the who were enrolled in the ongoing The-
0.22–16.77 mg/dL; p=0.044 and 3.52 mechanisms behind these risks have matically Organized Psychosis (TOP)
mg/dL, 95 percent CI, 0.31–6.69 mg/ not been determined. [Front Psychi- study, 280 (21.5 percent) of whom were
dL; p=0.031, respectively), while only atry 2014;5:137; J Clin Psychiatry treated with SSRIs. The SSRIs used
SSRI serum concentration was asso- 2014;75:46-61] by the participants were escitalopram
ciated with an elevation in triglyceride (n=154), citalopram (n=51), sertraline
levels (46.49 mg/dL, 95 percent CI, “[Patients with schizophrenia or bi- (n=40), fluoxetine (n=25), paroxetine
26.53–66.46 mg/dL; p<0.001). polar disorder], due to their underlying (n=8), escitalopram and citalopram
disease, have an increased risk of met- (n=1), and escitalopram and sertraline
SSRI serum concentrations and abolic disturbances, potentially making (n=1).
dose did not appear to affect high-den- them even more susceptible for such
sity lipoprotein (HDL) cholesterol, glu- adverse reactions caused by SSRIs,” The researchers believed that ana-
cose, or blood pressure levels, or waist said researchers of the present study. lysing the impact of both SSRI serum
circumference or body mass index. concentration and dose on metabolic
SSRI serum concentration was associ- “This study is the first to reveal sig- outcomes is one of the strengths of the
ated with the occurrence of metabolic nificant associations between SSRI use study.

25
DOCTOR | DECEMBER ISSUE
NEWSBITES

Longer duration of diabetes increases


fracture risk in women
STEPHEN PADILLA

T
ype 2 diabetes (T2D) is signifi-
cantly associated with an in-
creased risk of hip fracture, and
women with T2D for a decade have
more than 30 percent increased risk of
major osteoporotic fracture (MOF) and
more than 90 percent increased risk of
hip fracture than those without diabe-
tes, according to a recent study.

The results showed that the use of


conventional fracture risk assessment
tools (FRAX) failed to capture these el-
evated risks as they relate to duration
of disease.

“In a large study we found it was


long duration of diabetes that was more
important than the diagnosis itself in
predicting fracture risk, and that FRAX important in terms of understanding (1.93; 1.5 to 2.35) were significant-
underestimates risk in women with dia- and quantifying this increased risk,” re- ly underestimated by FRAX in those
betes,” researchers said. searchers said. with a diabetes duration longer than
10 years.
Women aged ≥40 years with 10 or FRAX-adjusted analyses showed
more years of prior healthcare cover- that only duration longer than 10 years The study has several limitations,
age undergoing hip dual-energy X-ray was associated with an increased risk such as the failure to distinguish type
absorptiometry measurements (1996 of MOF (hazard ratio [HR], 1.47; 95 1 from T2D, diagnoses of diabetes
to 2013) were identified using a clinical percent CI, 1.3 to 1.66), and this was based on administrative data, absence
dual-energy X-ray absorptiometry reg- similar in the fully adjusted models (HR, of any measures of glycaemic control
istry linked with the Manitoba admin- 1.34; 1.17 to 1.54). On the contrary, or measures of bone strength or qual-
istrative databases. Researchers ana- there was an increased risk of hip frac- ity as influenced by glycaemic control,
lysed each incident MOF and incident ture for all durations in a dose-depen- and the lack of detailed information
hip fractures over 7 years. dent fashion (eg, FRAX-adjusted HR, on smoking; physical activity; falls not
2.1; 1.71 to 2.59 for duration >10 y vs requiring hospitalization or mediators
A total of 8,840 women with and HR, 1.32; 1.03 to 1.69 for new onset). of falling such as hypoglycaemia; or
49,098 without diabetes were in- measures of diabetic complications
cluded in the study (31.4 percent “Indeed, at least 10 years of a di- such as neuropathy, myopathy, reti-
>10 y duration; 20.1 percent 5 to 10 agnosis with diabetes needed to be nopathy, or nephropathy; or chronic
y; 23.7 percent <5 y; 24.8 percent present before women were at a signifi- kidney disease.
new onset). [J Clin Endocrinol Metab cantly increased risk of MOF, whereas
2016;doi:10.1210/jc.2016-2569] the risk of hip fracture was increased “Lastly, our findings may lack gen-
even before the diagnosis of diabetes,” eralisability because the population was
“[W]e confirmed that type 2 diabe- according to researchers. drawn from one province in Canada
tes is a FRAX-independent risk factor and the subjects were predominantly
for MOF and hip fractures and demon- The MOF risk (calibration ratio, white, and we examined only women,”
strated that the duration of diabetes is 1.24; 1.08 to 1.39) and hip fracture risk researchers noted.

26
DOCTOR | DECEMBER ISSUE
NEWSBITES

Efficacy of pertussis vaccine wanes over time


ROSHINI CLAIRE ANTHONY

W
hile initially effective, the effi-
cacy of the pertussis vaccine
declines over time, particular-
ly in recipients of the acellular vaccine,
according to a Canadian study.

Vaccine effectiveness for individu-


als with up-to-date vaccination status
was 80 percent (95 percent confidence
interval [CI], 71-86 percent; p<0.05)
at 15-364 days postvaccination com-
pared with unvaccinated subjects. The
effectiveness increased slightly at 1-3
years (84 percent, 95 percent CI, 77-
89 percent; p<0.05), but decreased by
4-7 years postvaccination (62 percent,
95 percent CI, 42-75 percent; p<0.05).
Eight or more years after vaccination,
vaccine efficacy was 41 percent (95 per-
cent CI, 0-66 percent; nonsignificant). To assess the efficacy and duration “Vaccination in pregnancy is rec-
[CMAJ 2016;doi:10.1503/cmaj.160193] of immunity provided by the pertussis ommended in the US and the UK, and
vaccine, researchers used data from is likely an effective strategy to reduce
These findings were similar in par- 5,867 residents of Ontario, Canada disease in infants. Consideration should
tially vaccinated individuals (75, 68, and born between April 1992 and January also be given to introducing whole-cell
56 percent at 15-364 days, 1-3 years, 2013, 486 of whom tested positive vaccine for infant priming given the
and 4-7 years postvaccination, respec- for pertussis. Of these, 193 individuals observational data showing significant
tively; p<0.05 and 36 percent ≥8 years (39.7 percent) had up-to-date vaccina- long-term protective effects.”
postvaccination; nonsignificant) com- tion against pertussis, 134 (27.6 per-
pared with unvaccinated individuals. cent) were partially vaccinated, and 159


(32.7 percent) were unvaccinated. Of
Recipients of only the acellular form the control group (n=5,381), 62.9, 22.5,
of the vaccine were particularly affected and 14.6 percent were up to date, par-
by the reduction in efficacy with a 27 tially, and unvaccinated, respectively. “Vaccination in pregnancy
percent increased risk of testing pos- is recommended in the
itive for pertussis with each passing According to the authors, the re- US and the UK, and is
year postvaccination among those with sults of this study point to the need to
up-to-date vaccination status (adjusted reevaluate strategies for pertussis vac-
likely an effective strategy
odds ratio [adjOR], 1.27, 95 percent CI, cination as individuals aged ≤18 years to reduce disease in
1.20-1.34). They also had a higher risk in Ontario have only received the acel- infants. Consideration
of pertussis compared with individuals lular vaccine. should also be given to
who received at least three priming
doses of the whole-cell vaccine (adjOR, “Our finding that the low-effective-
introducing whole-cell
2.15, 95 percent CI, 1.30-3.57). ness whole-cell vaccine is still better for vaccine for infant priming
priming than the currently used acellu- given the observational
“Our results showed that receiving lar vaccine nearly 2 decades after the data showing
one or more doses of whole-cell vac- change in practice has profound im-
cine as an infant provided significant plications for understanding the effec-
significant long-term
protection from pertussis more than a tiveness of the pertussis vaccine,” they protective effects”
decade later,” said the study authors. said.

27
DOCTOR | DECEMBER ISSUE
www.mims.com MIMS mobile/tablet app facebook.com/mimscom

MIMS-mDrugs206x276-0816.indd 1 24/8/16 2:18 pm


NEWSBITES

Hypertension more prevalent in Chinese children


STEPHEN PADILLA allow comparisons among different

T
age groups and survey years. Nation-
he prevalence of hypertension
al and international age-specific and
in Chinese children, adjusting
height-specific references were used to
for height, grew by 0.19 percent
define prehypertension and hyperten-
per year on average over the past two
sion rates.
decades, which is much less than that
reported in previous researches, ac-
Systolic and diastolic blood pres-
cording to a recent study. This trend is
sures increased 0.07 and 0.09 SD per
consistent with the obesity trend and
survey year, respectively. Body mass
appears regardless of sex and area.
index, waist circumference and height
increased 0.14, 0.11 and 0.29 SD, re-
Researchers re-evaluated the secu- spectively.
lar trends of blood pressure and hyper-
tension prevalence in Chinese children The general obesity prevalence
and adolescents by adjusting for grow- rose to 8.1 from 1.5 percent (p≤0.0001
ing body sizes. They obtained data for trends), with an average annual in-
from the China Health and Nutrition crease (AAI) of 0.36 and 0.42 percent sion was threefold higher among boys
Survey (1991 to 2011), which included for urban and rural boys, respectively, (0.29 percent) than among girls (0.09
7,358 boys and 6,881 girls aged 8 to and of 0.33 and 0.22 percent for urban percent), explaining the sex difference
17 years. [J Hypertens 2016:34:2337- and rural girls, respectively. in the rural population.
2343]
The hypertension prevalence rose Researchers noted that even af-
National references were used to to 10.7 from 6.9 percent (p≤0.0001 for ter applying the international criteria,
standardize body size measurements trends), with an average AAI of 0.19 the area and sex differences in AAI re-
and blood pressure into z-scores to percent. The overall AAI in hyperten- mained.

Comorbidities influence
antiplatelet therapy adherence
ROSHINI CLAIRE ANTHONY In contrast, individuals with diabetes Individuals who were taking vitamin

C
(HR, 1.74, 95 percent CI, 1.11–2.73) K antagonists were at a higher risk of
omorbidities such as diabetes,
and hypercholesterolaemia (HR, 1.43, stopping any antiplatelet therapy (HR,
hypercholesterolaemia, and hy-
95 percent CI, 1.12–1.83) who were 18.97, 95 percent CI, 16.91–21.28).
pertension, and a recent inci-
taking clopidogrel had a higher risk of
dence of myocardial infarction (MI) may
antiplatelet discontinuation (all p<0.05). “As the concomitant use of an anti-
influence a patient’s adherence to anti-
[Br J Clin Pharmacol 2016;doi:10.1111/ platelet drug and an oral anticoagulant
platelet therapy, a recent study shows.
bcp.13139] is associated with bleeding, this com-
bination should be avoided. However,
Individuals with hypertension (haz- Individuals who had an MI more there are indications, such as for those
ard ratio [HR], 0.69, 95 percent confi- recently were less likely to discontinue with atrial fibrillation undergoing coro-
dence interval [CI], 0.52–0.93), diabetes any antiplatelet therapy (HR, 0.38, 95 nary stenting, in whom the combination
(HR, 0.52, 95 percent CI, 0.37–0.72), percent CI, 0.19–0.77 for MI occurring is indicated,” said researchers.
and hypercholesterolaemia (HR, 0.45, in 2008–2010 and HR, 0.69, 95 per-
95 percent CI, 0.33–0.60) who were cent CI, 0.61–0.79 for MI occurring in In this retrospective study from the
taking aspirin had a lower risk of anti- 2003–2007 compared with MI occurring Netherlands, subjects were 4,690 pa-
platelet discontinuation following an MI. in 2002 or earlier; p<0.05). tients (aged ≥18 years) from the Utrecht

29
DOCTOR | DECEMBER ISSUE
NEWSBITES

Cardiovascular Pharmacogenetics co- months after the first MI, a recurrent haps had more MIs or a greater degree
hort who had been hospitalized for their ACS occurred within 6 months after the of cardiac dysfunction after their MI.
first MI between 1986 and 2010 and discontinuation date,” they said. These comorbidities are also risk fac-
followed up for up to 10 years (median tors for other cardiovascular diseases
5.6 years) after being discharged from Researchers did not account for the such as strokes or peripheral arterial
hospital. reasons behind antiplatelet discontinu- disease. As these patients have expe-
ation, which they said was an area for rienced more complications of these
Information on drug therapy was future research. They also did not iden- diseases than a similar patient with-
obtained from the Pharmaco-Morbidity tify if treatment discontinuation was ini- out these comorbidities, they may be
Record Linkage System database. In- tiated by the patient or physician. motivated to be more compliant with


dividuals prescribed antiplatelets were medications like antiplatelets so as to
divided into three groups, ie, persistent reduce the chance of recurrent events,”
users (gap between prescriptions ≤90 he said.
days), nonpersistent users (>90-day “Patients need to
gap with no refills), and restarters (new understand the reasons “Because these patients may also
prescription filled after >90-day gap). and rationale behind a be seeing physicians more frequently
for management of these comorbid-
doctor recommending
The number of persistent users of ities, the degree of compliance may
antiplatelet drugs reduced from the a treatment” be greater as they are frequently being
1-year follow-up to the 10-year fol- asked about medication adherence,”
low-up (84 percent vs 32.8 percent). said Chin.
However, many of the patients who
stopped taking antiplatelets later re- According to Assistant Professor According to Ho, antiplatelet non-
sumed therapy, with 89.3 percent of Ho Kay Woon, a senior consultant at persistence is a problem in Singapore.
patients on antiplatelets at 10 years the Department of Cardiology, Na- “Noncompliance to medication or fol-
post-MI. tional Heart Centre Singapore (NHCS) low-up are common even amongst pa-
who was not affiliated with the study, tients with prior MI,” he said.
For individuals on aspirin, per- patients with the above comorbidities
sistence was 77.3 percent at 1 year will more likely need other medications “Medication adherence and com-
versus 27.5 percent at 10 years (over- for their treatment. Thus, there is likely pliance can be improved by patient
all use of aspirin at 10 years was 77.1 to be longer chronic disease follow-up education and reinforcement. Patients
percent after accounting for restarters), with their family practitioner and hence, need to understand the reasons and
while clopidogrel persistence was 39 a greater likelihood of persistence with rationale behind a doctor recommend-
percent at 1 year (26 percent overall us- antiplatelet agents. ing a treatment. Similarly, the physician
ers at 6 years after including restarters). must be sensitive and aware of possible
Dual antiplatelet therapy persistence Assistant Professor Chin Chee reservations that the patient may have,
was 31.5 percent at 1 year with many Tang, a senior consultant at the same specifically, the patient should be made
nonpersistent users switching to single institution, agrees. “Patients with these aware of possible side effects that they
therapy. comorbidities are likely to have more may encounter and so not be alarmed
severe ischaemic heart disease, per- if they do occur,” said Chin.
“In spite of the restart, it is important
to be aware that the gap between dis-
continuation and restart is a critical peri-
od for the occurrence of recurrent [car-
diovascular] events,” said researchers.

“A discontinuation of antiplatelet
drugs early after [coronary heart dis-
ease] and [percutaneous coronary
intervention] might lead to a recur-
rent [acute coronary syndrome (ACS)]
event. The present study showed that
in 30 percent of the patients who dis-
continued antiplatelet drugs within 6

30
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | Q & A

Postnatal depression:
Q & A with perinatal
psychiatrist Dr Helen Chen

P
earl Toh spoke with Dr Helen - Feelings of hopelessness
Chen, head and senior consul- - Sleep disturbance unrelated to baby’s
Dr. Helen Chen Yu
tant of the Department of Psy- needs
chological Medicine at KK Women’s - Thoughts of harm to self or baby, or
and Children’s Hospital (KKH) in Sin- suicide
gapore on factors affecting postnatal
depression (PND) and how clinicians In PND, there is usually a combi-
can help their patients cope with this nation of these symptoms lasting for
condition. 2 weeks or longer, with significant im-
  pact on the mother’s functioning – for
What is the prevalence of example, she is unable to tend to the
PND among mothers in needs of her baby, or handle her daily
Singapore? activities.
The prevalence of PND in Singa-  
pore is about 7 percent, when consid- Your recent study
Dr Helen Chen, head ering both milder forms as well as more showed that women
and senior consultant severe forms of depression. who experienced
of the Department of   persistent childbirth
Psychological Medicine How is PND usually pain after delivery had
diagnosed? an increased risk of
at KK Women’s and Diagnosis is generally done by clin- PND. [World Congress of
Children’s Hospital (KKH) ical assessment by trained profession- Anaesthesiologists 2016,
in Singapore, talks about als, or using structured interview tools. abstract PR 196] What
factors affecting PND Screening tools, such as the Edinburgh are the major factors
and how clinicians can Postnatal Depression Scale, can also that might contribute to
help their patients cope help identify those that are likely cas- PND besides persistent
es. As there can be false positives or childbirth pain?
with this condition. false negatives from the screening, an Various factors can contribute to
assessment is typically recommended PND – usually, it is an interplay of fac-
if the woman is symptomatic. tors for each woman. Major risk factors
  of PND include history of depression,
What are the symptoms and positive family history of PND (the
Scan the to look out for that should risk of PND is increased twofold if her
QR code to alert the doctor that the mother or sister had PND).
view more of patient might be having
MIMS clinical PND? Other factors would be concurrent
news Some common signs and symp- stress factors such as marital prob-
toms of PND include: lems, work-related stress, issues with
in-laws or available support. Early
- Low mood motherhood is not easy, especially with
- Crying sleep deprivation, and challenges of
- Irritability breastfeeding, so exhaustion can set in
- Appetite changes and contribute to PND.
- Loss of energy
- Poor concentration or forgetfulness Women who experienced poor
- Excessive self-blame or guilt maternal care during childhood will

31
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | Q & A

es might be due to hormonal change to care well for their infants. Evidence
alone, so they prefer to wait for things has shown that mothers who are de-
to settle. But if it is so, then we should pressed tend to be less attuned to the
expect to see 100 percent of women needs of their infants, and are less able
getting depressed, because everyone to stimulate their infants, and this there-
experiences hormonal changes with fore affects their emotional and cogni-
delivery. Rather, it is because wom- tive development.
en are more vulnerable at this time
when their bodies are going through Mothers often fear getting help be-
tremendous physical changes so that cause they think medications are harm-
any added stress can tip them into ful, especially if they are breastfeeding,
depression. or they fear others thinking they are
  mad or of unsound mind.
In Singapore, what are
the current support To reassure my patients, I often
system/programmes share that PND is a medical condition
available for mothers to that is caused by brain neurotransmitter
cope with or to reduce imbalance due to various stress factors
persistent childbirth as mentioned above, just like diabetes
pain physically and is caused by insulin imbalance. Also,
psychologically? medication can be chosen for mothers
Prompt and adequate pain control to safely nurse their babies – indeed,
is most effective in ensuring mothers mothers who are depressed tend to
do not experience persistent child- stop breastfeeding prematurely, and
birth pain. The experience of pain is stress can actually hamper their milk
also often influenced by the psycho- production and milk let-down. Impor-
logical state of the mother, as our re- tantly, our mainstay of intervention is
search has clearly shown, so holistic supportive counselling and therapy,
care that incorporates emotional sup- whilst medication is only necessary for
port addressing the individual needs those with at least moderately severe
is important. depression.

also be at risk – because the difficult At KKH, we have been running For doctors, I think it is common
emotional memories that have been the PND Intervention Programme for them to fear asking how moth-
repressed can surface at this time of since 2008 – this programme pro- ers are feeling, lest she says she is
transition, and present as an internal vides free emotional health screening depressed and suicidal but refuses
stress, wherein they doubt themselves, for postnatal women and identifies to accept a referral to get help. So I
or feel too broken to be good enough early those who need psychological usually advise that it is alright if the
mothers. support. Depending on the nature or mother refuses – the burden is not on
severity of their emotional distress, the doctor who asked to ensure, just
Difficult or traumatic labour experi- women are then offered supportive as it is with any screening procedure.
ence can also contribute to post-trau- counselling, support group inter- Nonetheless, the doctor can and
matic stress symptoms and PND. This vention, psychiatric intervention, or should give advice to a mother who is
is not an uncommon reason for women psychological therapy. Our postnatal depressed to get help – and perhaps
to delay or avoid a subsequent preg- patients are screened for severity of some days later, she might decide to
nancy. pain, and patients with persistent pain call the helpline.
will be referred to a specialist for fur-
Personality types that predispose ther assessment. It is also helpful not to say to a
women to PND include especially those   mother “you are depressed, you need
who have anankastic traits – ie, being What advice would you to see a psychiatrist”, as this typically
rigid or perfectionist. give doctors or mothers invites a defensive response. Instead,
facing PND? say “I wonder if you would like some
Women and their families often Early intervention is crucial, as PND help – you might be suffering from
think that postnatal emotional chang- can impact on the capacity of mothers depression.”

32
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | IN PRACTICE

Managing acne in primary care

A
cne is a chronic inflammatory [J Am Acad Dermatol 2009;60:S1-50.
disorder of the pilosebaceous doi:10.1016/ j.jaad.2009.01.019; Euro-
unit. It often starts with excess pean Dermatology Forum Guidelines for
sebum production and abnormal shed- Dermatology in Europe 2009]
ding of skin cells. Bacteria that feed on
the sebum then proliferate and lead to In 2015, a group of dermatolo-
Dr Tan Lixian Chris
inflammation. gists from Southeast Asia jointly de-
veloped a set of treatment guidelines
Adolescents are most at risk of de- to aid physicians in managing acne in
veloping acne. In a community-based Southeast Asian patients. [J Dermatol
cross-sectional study of 1,045 adoles- 2015;42:945-953]
cents in Singapore aged 13-19 years,
88 percent of those surveyed identified There are several different types of
themselves as having acne. [Br J Der- acne:
matol 2007;157:547-551] • Cosmetic Acne: This describes
an association between the use of cos-
This is comparable to international metic products and acne, a phenom-
data where up to 90 percent of adoles- enon attributed to follicular plugging
cents have some form of acne. induced by certain agents. Patients
present with insidious, slow develop-
GPs are often the first point of ment of the small bumps of skin called
contact in disease management and comedones (whiteheads and black-
health promotion for the majority of heads) and, eventually, inflammatory
our population. They have built trust- lesions. In addition, follicular irritation
ing patient-doctor relationships within related to the application of cosmetics
the community that they serve. Hence, may result in the rapid appearance of
they have the access and confidence to small inflammatory papules.
identify and initiate early acne treatment • Acne excoriée: A scarring acne
measures in patients who visited them condition often, but not always, seen
even for a different ailment initially. in young women. Relatively mild acne
Acne is a chronic comedones or inflammatory papules
Diagnosing acne are chronically and obsessively picked
inflammatory skin
Acne requires a clinical diagnosis and excoriated, leading to erosions and
disorder that results in and the spectrum of acne lesions rang- scarring. An underlying psychiatric dis-
skin blemishes. Primary es from noninflammatory open or closed order can be associated, and treatment
care doctors are likely comedones (blackheads and white- may involve antidepressants and psy-
the first point of contact heads) to inflammatory lesions, which chotherapy.
for those with acne. may be papules, pustules, cysts or nod- • Post Adolescent Acne: Acne oc-
ules. The presence of excoriations, post curring in individuals in adulthood, typ-
Radha Chitale spoke
inflammatory hyperpigmentation, and ically after the age of 25. This type of
with Dr Tan Lixian Chris, scars should also be noted. Lesions acne affects females more often than
an associate consultant can also occur on the neck, chest, up- males. Clinical signs and symptoms
in the Division of per back, and upper arms, in addition are similar to conventional adolescent
Dermatology at to the face which is the most common. acne. However, a minority of patients
National University Internationally accepted guidelines pub- may also present with hirsutism, seb-
lished by the Global Alliance for Acne orrhoea and coarse skin, suggesting an
Hospital, Singapore,
can be a useful guide for GPs in man- underlying hyperandrogenic state.
about how GPs can aging their patients. The American and • Acne fulminans: The presence
best diagnose and treat European academies of dermatology of fever and joint pain with an acute
patients with acne. have also published similar guidelines. eruption of large inflammatory nodules

33
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | IN PRACTICE

and friable plaques with haemorrhagic and are anti-inflammatory. Retinoids are cy of application. Care should also be
crusts. This rare condition affects ado- ideal for comedonal acne and, when taken to assess the risk-benefits when
lescent males primarily. Lesions usually used in combination with other agents, prescribing COCs and strict contracep-
involve the trunk, but may be present for all acne variants. tion measures must be taken in women
elsewhere. of child-bearing age treated with oral
• Acne conglobata: Acne conglo- BP is an antibacterial agent that kills isotretinoin.
bata is a severe form of nodular acne acne-causing bacteria through the re-
that is most commonly seen in young lease of free oxygen radicals and is also Although there are studies that
males. Lesions are most prominent on mildly comedolytic. No resistance to show efficacy in complementary treat-
the back, chest, and buttocks, but can this agent has been reported, and the ments such as chemical peels and light
also appear in other sites. Large drain- addition of BP to regimens of antibiotic therapy, there is limited evidence to
ing lesions, sinus tracts, and severe therapy enhances results and may re- routinely recommend these therapies
scarring may occur. Systemic symp- duce resistance development. BP with to all patients.
toms are absent. retinoid combination is a convenient
once-a-day application that has shown There is also emerging but limited
GPs should be aware of and dis- high efficacy and tolerability in treating evidence that diet plays a role in the
tinguish between other conditions that mild and sometimes even moderate pathogenesis of acne.
may have similar clinical features to acne.
acne. This is because these patients GPs should refer patients to a
may not respond well to conventional Moderate and severe acne would specialist if they are unsure of the di-
acne therapies. These conditions in- usually require the addition of systemic agnosis, if patients have poor or no
clude rosacea, perioral dermatitis, and therapies to topical therapies. Evidence response to therapy, if complications
pityrosporum folliculitis. A detailed clin- supports the efficacy of systemic antibi- such as allergies or contact dermatitis
ical history and thorough physical ex- otics like tetracycline, doxycycline, mi- arise from therapy, if the acne is severe
amination of the skin will help, as will nocycline, trimethoprim/sulfamethox- with systemic manifestations of signif-
keeping up with current medical knowl- azole (TMP/SMX), erythromycin and icant scarring and abscess formation,
edge. azithromycin. Combination oral con- and if the acne is associated with hy-
traceptive pills (COCs), anti-androgens perandrogenism (eg, hirsutism).
Treating acne like spironolactone and oral isotretinoin
After making the diagnosis and are also used. Conclusion
identifying the relevant aggravating fac- The highest incidence of acne oc-
tors (eg cosmetic products, habitual Importantly for GPs to note, topical curs in adolescents, a group that is
excoriations, etc), GPs should deter- or systemic antibiotics should not be highly conscious of their physical ap-
mine the severity of the acne and treat used as monotherapy to prevent risks pearance. Hence, acne poses signifi-
accordingly. Therapy choice may also of Propionibacterium acnes antibiotic cant stress to their self-esteem and can
be influenced by age of the patient, resistance. They should be used judi- lead to social withdrawal and isolation.
comorbid medical conditions, site of in- ciously in combination with non-anti- Even adults can have conspicuous
volvement, and patient preference. biotic preparations such as BP and acne, which makes patients self-con-
retinoids. In the case of systemic an- scious and depressed in severe cases.
Mild acne is typically treated with tibiotics, concurrent use of topical BP Diagnosing and treating acne as early
topical therapies alone. These include and retinoids help limit the duration of and as accurately as possible can help
benzoyl peroxide (BP), salicylic acid, systemic antibiotic use to the shortest minimize severe progression and per-
antibiotics, combination antibiotics with possible duration, typically 3 months. manent scarring.
BP, retinoids, retinoid with BP and aze-
laic acid. Recommended first line topi- GPs should be mindful of drug al-
cal therapies for mild acne include ret- lergies and tolerability to acne medi-
inoids alone or combination therapies cations. For example, topical retinoids
such as retinoid with BP, antibiotic with may cause irritation in people with
Online resources
BP, or all three combined. eczema and generally sensitive skin. American Academy of Dermatology - www.aad.org
However, this can be prevented by European Dermatology Forum - www.euroderm.org
Topical retinoids are vitamin A de- measures such as addition of a regular European Academy of Dermatology and Venerology
www.eadv.org
rivatives. They are comedolytic, resolve moisturizer, using a more gentle facial Asian Academy of Dermatology and Venerology
the precursor microcomedone lesion, cleanser, and reducing the frequen- www.asianderm.org

34
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | DEVICE

Skin patch safe, promising


for treating peanut allergy
PEARL TOH and 130 mg in the VP100 (p=0.014) and

D
VP250 (p=0.003) groups, respectively.
elivery of peanut protein through Significant increases were observed in
the skin by means of a wearable both peanut-specific IgG4 levels and
skin patch, an approach known IgG4/IgE ratios (p<0.0001 for both) be-
as epicutaneous immunotherapy, is tween treatment and placebo groups.
safe and shows promise for treating There were also trends toward reduced
peanut allergy, especially in young peanut specific TH2 cytokines (p=0.059
children, according to interim results for interleukin [IL]-4 and p=0.04 for IL-
of an ongoing study. “Despite active 13) and basophil activation.
avoidance, the risk of an adverse re-
action from exposure is ongoing,” said “The trends seen in both basophil
Epicutaneous immunotherapy using a skin researchers, who noted that peanut and T-cell responses suggest that ex-
patch safely induced treatment response in allergy presents the most common posure to peanut through intact skin
young children in the study.
life-threatening food allergy. “An effec- might modulate TH2 responses and
tive treatment for peanut allergy would basophil reactivity,” researchers said. 
be highly desirable.”    Compliance with treatment was high
(97.1 percent of doses), suggesting
The multicentre, double-blind, that the patch was convenient and well
phase II trial randomized 74 individuals tolerated.
(aged 4–20 years, median 8.2 years)
with peanut allergy to placebo (n=25), Although patch-site reactions oc-
100 µg (VP100; n=24) or 250 µg curred more frequently in the treat-
(VP250; n=25) peanut immunotherapy ment groups (79.8 percent of VP100
delivered through a skin patch known and 79.7 percent of VP250 doses)
as Viaskin Peanut. The participants compared with placebo (14.3 percent;
were assessed for treatment success, p=0.003), most were mild (≤grade 2).
which referred to success in a 5,044 mg Reactions extending past the patch
protein oral food challenge or achieve- area occurred in 8.9 percent of VP100
ment of ≥10-fold increase in success- and 16.2 percent of VP250 doses
fully consumed dose (SCD) of protein at compared with 1.5 percent of place-
week 52 compared with baseline. [J Al- bo dose, while nonpatch-site reactions
lergy Clin Immunol 2016;doi:10.1016/j. were uncommon (0.2 and 0.1 percent
jaci.2016.08.017] Compared with pla- of VP100 and VP250 doses vs 0.2 per-
cebo (12 percent), there were more par- cent of placebo dose).
ticipants in the VP100 group (46 per-


cent; p=0.005) and VP250 group (48 “Additional time on therapy is need-
percent; p=0.003) who had achieved ed to determine whether the modest
treatment success at week 52. clinical changes noted will be enhanced
“Peanut allergy presents after a longer duration of therapy and
the most common Treatment success was significantly will provide clinically meaningful protec-
life-threatening food higher among younger children (aged tion from anaphylaxis,” said research-
allergy. “An effective ≤11 years) compared with those older ers, who were awaiting further results
than 11 years (61 percent; p=0.0003 for at 130 weeks of the study. 
treatment for peanut VP250 and 59 percent; p=0.0006 for
allergy would be highly VP100 versus 6 percent for placebo).
desirable” SCD also changed significantly from 0
mg of protein in the placebo to 43 mg

35
DOCTOR | DECEMBER ISSUE
CLINICAL INSIGHTS | DEVICE

HIV test on USB stick:


Is it ready for clinic use?
ELVIRA MANZANO vice. Heaters and thermal sensors are

S
imbedded in the chip to detect HIV-1
cientists in the UK have devel- viral load without the need for addition-
oped a USB stick that can ac- al power supply, labels, or fluorescence


curately test for viraemia in less detection.
than 30 minutes among individuals with
suspected human immunodeficiency
virus (HIV). A drop of blood placed onto
“Viral load is the
the USB stick is all they need to pro-
duce results. earliest marker of
HIV infection”
Current HIV tests in the market take
at least 3 days and involves sending
The device can diagnose HIV in less than 30 of blood samples to the laboratory for
minutes and with 95 percent accuracy in the analysis. In poor-resourced settings Screening of 991 clinical samples –
initial trial.
with high HIV burden, access to those 164 on the chip – yielded a sensitivity
tests is even limited. of 95 percent (in vitro) and 88.8 per-
cent (on chip) at >1000 copies/reac-
“Our HIV specific pH-LAMP assay, tion across a broad spectrum of HIV-1
coupled with novel CMOS technology, viral clades. Median time to detection
shows great potential as a route to a was 20.8 minutes in samples with
point-of-care diagnostic suitable for >1000 copies RNA. [Scientific Reports;
use in clinical settings without access doi:10.1038/srep36000]
to a laboratory infrastructure,” said
study author Dr Graham Cooke from Viral load is the earliest marker of
the Department of Medicine at Imperial HIV infection and a high viral load is
College London, UK. related to seroconversion symptoms.
According to the World Health Orga-
The test can also detect viraemia in nization (WHO), detection of viral loads
HIV-infected individuals receiving antivi- >1000 copies/mL is enough to estab-
ral treatment as well as identify multiple lish sufficient sensitivity. [Antivir Ther
pathogens. 2008; 13;1-13]

Regular monitoring of viral load The authors said the 95 percent


is crucial to the success of any HIV detection rate for the LAMP reaction at
treatment, so is detection of treatment >1000 copies/reaction is “encourag-
failure. Current methods often require ing.” However, more studies are war-
costly and complex equipment that ranted before the test can be used in
can take days to produce a result, said the clinic. “Further development is re-


Cooke. “We have taken the job done quired, including an evaluation of spec-
by this equipment, which is the size of ificity across a wide range of clinical
a large photocopier, and shrunk it down isolates.”
“The RT pH-LAMP is to a USB chip.”
based on a novel CMOS The device was created by Cooke’s
chip platform and The RT pH-LAMP is based on a team at the Imperial College London
novel CMOS chip platform and uses and the privately-held US firm DNA
uses a drop of blood a drop of blood to detect HIV – it then Electronics, with funding from The Na-
to detect HIV” creates an electrical signal that is read tional Institute for Health Research Im-
by a computer or any handheld de- perial Biomedical Research Centre.

36
DOCTOR | DECEMBER ISSUE
CALENDAR

DECEMBER DECEMBER FEBRUARY

03-06
SATURDAY - TUESDAY
16-19
FRIDAY - MONDAY
20-24
MONDAY - FRIDAY

58th American Society of European Society for Medical 26th Conference of the Asian
Hematology Annual Meeting Oncology (ESMO) Asia 2016 Pacific Association for the Study
& Exposition Congress of the Liver (APASL) 2017
Location: San Diego, California, US Location: Singapore Location: Shanghai, China
Tel: 202 776 0544 Tel: +41 (0)91 973 19 39 Tel: +81-3-6380-0102
Website: http://www.hematology.org/ Email: http://www.esmo.org/Contact-Us Email: info@apasl2016.org
Annual-Meeting/ Website: http://www.esmo.org/Conferences/ Website: http://www.apasl2016.org/conf_
ESMO-Asia-2016-Congress contact.html

MARCH MARCH MARCH

01-03
WEDNESDAY - FRIDAY
02-04
THURSDAY - SATURDAY
10-12
FRIDAY - SUNDAY

Bangkok International 4th International Conference on Highlights of ASH 2017 –


Neonatology Symposium: 2017 Nutrition and Growth Asia Pacific
Location: Bangkok, Thailand Location: Amsterdam, The Netherlands Location: Hong Kong
Tel: +46 40 33 24 15 Tel: + 41 315 280 432 ext. 50 Tel: 001 202-776-0544
Email: www:bkkneonatology.com Fax: + 41 22 906 9140 Email: customerservice@hematology.org
Website: http://med.mahidol.ac.th/en/news/ Website: http://2017.nutrition-growth.kenes. Website: http://www.hematology.org/High-
conference/16112016-1113-en com/ lights/Asia/3544.aspx

MARCH MARCH MARCH

17-19
FRIDAY - SUNDAY
20-22
MONDAY - WEDNESDAY
23-26
THURSDAY - SUNDAY

66th Annual Scientific Session Royal College of Obstetrics & 11th World Congress on
of the American College of Gynaecology (RCOG) World Controversies in Neurology
Cardiology (ACC) 2017 Congress 2017 (CONy) 2017
Location: Washington DC, US Location: Cape Town, South Africa Location: Athens, Greece
Tel: 202-375-6000, ext. 5603 Tel: +27 31 368-8000 Tel: +27 31 368-8000
Email: resource@acc.org Fax: +27 31 368-6623 Fax: +27 31 368-6623
Website: https://accscientificsession.acc. Email: Gills@turnersconferences.co.za Email: cony@comtecmed.com
org/ Website: http://rcog2017.com/Registration. Website: http://www.comtecmed.com/
asp cony/2017/

37
DOCTOR | DECEMBER ISSUE
MIMS COMMUNITY

Trending on MIMS Community

“Just a nurse”: Too Busy for exercise What is the strangest


A nurse speaks up “No time to exercise” is one of thing you have heard
against her profession the most common statements a patient say?
being devalued when doctors stress the need for Many patients come into the
A Queensland nurse’s regular exercise. Doctors have a clinic or hospital with some
impassioned Facebook post responsibility to do a better job bizarre misconceptions about
hitting back at people belittling of pointing out the necessity of their health. What is the strangest
her profession has gone viral. Our physical activity to prevent med- thing you’ve heard your patients
very own community of doctors, ical complications. How do you say?
nurses and pharmacists chime in stress the need for exercise to a
on the discussion and share how patient who claims to be busy?
nurses should be valued.

49 Comments 47 Comments 42 Comments

The challenges of Was there one patient


treating transgender that made your
patients years of education
Transgender is basically an all worth it? Want to take part in the
umbrella term that is used for Share with us your most mem- MIMS Community
individuals with gender identifi- orable experience with a patient discussions regarding
cation different from the gender and how this particular patient medical news and
healthcare?
given them during birth. They has brightened your outlook on
face several challenges as far as career and life! Join our growing
health care is concerned due to community
their specific unique needs. of healthcare
professionals to share
your learnings and
network with your
peers.

25 Comments 20 Comments

www.mims.com

38
DOCTOR | DECEMBER ISSUE